Dupilumab in Eosinophilic Esophagitis Refractory to Conventional Management in Pediatrics: Report of Two Cases / Dupilumab en esofagitis eosinofílica refractaria al manejo convencional en pediatría: reporte de dos casos

Abstract Introduction: This publication aims to show the clinical, endoscopic, and histological responses of two pediatric patients who received dupilumab as a management strategy for eosinophilic esophagitis. Dupilumab is a monoclonal antibody that inhibits the alpha chain of the interleukin (IL)-4 and IL-13 receptors involved in the Th2 inflammatory response. The potential therapeutic role of this biological drug has been demonstrated in pediatric clinical trials in other allergic pathologies, such as atopic dermatitis and asthma, with an adequate safety and effectiveness profile. Clinical cases: Two children with a personal history of atopy, allergic rhinitis, asthma, atopic dermatitis, and food allergy began with gastrointestinal symptoms that confirmed the diagnosis of eosinophilic esophagitis. Despite the different management strategies, adequate control of the disease was not achieved, and it is considered that they benefited from management with dupilumab due to the disease evolution and the coexistence of uncontrolled atopic dermatitis. Conclusions: In recent years, various management strategies in pediatrics have been published, particularly high-dose proton pump inhibitors, topical corticosteroids, and elimination diets. However, despite these strategies, at least one-third of patients may fail to achieve remission with initial treatment, making this entity a therapeutic challenge for the gastroenterologist and pediatric allergist. Our patients received the dose recommended for their weight and age and approved for asthma and atopic dermatitis, resulting in clinical and histological remission. The improvement in gastrointestinal symptoms was accompanied by better control of asthma, rhinitis, and dermatitis. None of the patients had adverse effects of the medication.

Resumen Introducción: El objetivo de esta publicación es mostrar la respuesta clínica, endoscópica e histológica de dos pacientes pediátricos que recibieron dupilumab como estrategia de manejo para esofagitis eosinofílica. El dupilumab es un anticuerpo monoclonal que inhibe la cadena alfa del receptor de las interleucinas 4 y 13, involucradas en la respuesta inflamatoria Th2. El potencial rol terapéutico de este medicamento biológico se ha demostrado en ensayos clínicos en pediatría en otras patologías alérgicas como la dermatitis atópica y el asma, y ha mostrado un adecuado perfil de seguridad y efectividad en pediatría. Casos clínicos: Se trata de dos niños con antecedentes personales de atopia, rinitis alérgica, asma, dermatitis atópica y alergia alimentaria, que inician con síntomas gastrointestinales que conducen a confirmar el diagnóstico de esofagitis eosinofílica, en quienes a pesar de las diferentes estrategias de manejo no se logra un adecuado control de la enfermedad, y se considera que se benefician del manejo con dupilumab por la evolución de la enfermedad, así como la coexistencia de dermatitis atópica no controlada. Conclusiones: En los últimos años se han publicado diferentes estrategias de manejo en pediatría, entre los que se destaca el uso de inhibidores de la bomba de protones a dosis altas, corticoides tópicos y las dietas de exclusión; sin embargo, a pesar de estas estrategias, al menos un tercio de los pacientes puede fallar en lograr la remisión con el manejo inicial, lo que convierte a esta entidad en un reto terapéutico para el gastroenterólogo y el alergólogo pediatra. Nuestros pacientes recibieron la dosis recomendada para su peso y edad aprobada en asma y dermatitis atópica, y se logró la remisión clínica e histológica. La mejoría de los síntomas gastrointestinales se acompañó de un mejor control del asma, la rinitis y la dermatitis. Ninguno de los pacientes tuvo efectos adversos al medicamento.

Beyond the Gut: Extraintestinal Manifestations of Inflammatory Bowel Disease in Children and Adolescents / Más allá del intestino: manifestaciones extraintestinales de la enfermedad inflamatoria intestinal en niños y adolescentes

Abstract Background: Extraintestinal manifestations (EIM) are common in children and adults and their presence is associated with a higher severity of inflammatory bowel disease (IBD). In pediatrics, studies are scarce in Latin America and do not exist in Colombia. Objective: To describe the prevalence of EIM in children with IBD and the associated demographic, clinical, and biochemical characteristics. Methodology: Retrospective study of patients diagnosed with pediatric-onset IBD between 2007 and 2022 treated at an institution in Bogotá. A descriptive analysis was performed and in the groups with and without EIM clinical and biochemical variables were compared using Fisher's exact test, Student's T, and Mann-Whitney's U. Results: Of 71 confirmed cases, 45% had typical ulcerative colitis, 27% Crohn's disease, 7% atypical ulcerative colitis, 1.4% colonic Crohn's, and 20% unclassifiable IBD. Thirteen patients (18%) had at least one EIM, and mucocutaneous was the most frequent (58%). The time from symptoms onset to diagnosis was higher in the EIM group (13.2 years vs. 10.2 years; p = 0.02). Nocturnal diarrhea, hyporexia, and weight loss were more frequent in children with EIM. The EIM group showed lower hemoglobin levels, and higher globular sedimentation rate, and received biologics more frequently (38% vs. 23%, p = 0.2). Conclusions: The frequency of MEI in this series is similar to that reported in the literature; its presence is associated with higher disease severity, higher frequency of biological use, and longer time IBD diagnosis.

Resumen Antecedentes: Las manifestaciones extraintestinales (MEI) son comunes en niños y adultos y su presencia se asocia con mayor gravedad en la enfermedad inflamatoria intestinal (EII). En pediatría, los estudios son escasos en Latinoamérica y no existen en Colombia. Objetivo: Describir la prevalencia de las MEI en niños con EII y las características demográficas, clínicas y bioquímicas asociadas. Metodología: Estudio retrospectivo de pacientes diagnosticados con EII de inicio pediátrico entre 2007 y 2022 atendidos en una institución en Bogotá. Se realizó un análisis descriptivo y en los grupos con y sin MEI se compararon variables clínicas y bioquímicas por medio de la prueba exacta de Fisher, T de Student y U de Mann-Whitney. Resultados: De 71 casos confirmados, el 45 % tenía colitis ulcerativa típica, el 27 % enfermedad de Crohn, el 7 % colitis ulcerativa atípica, el 1,4 % Crohn colónico y el 20 % EII no clasificable. 13 pacientes (18 %) presentaron al menos una MEI, y las mucocutáneas fueron las más frecuentes (58 %). El lapso desde el inicio de los síntomas hasta el diagnóstico fue mayor en el grupo MEI (13,2 años frente a 10,2 años; p = 0,02). La diarrea nocturna, la hiporexia y la pérdida de peso fueron más frecuentes en niños con MEI. El grupo MEI mostró niveles más bajos de hemoglobina, más elevados de velocidad de sedimentación globular y recibieron biológicos con mayor frecuencia (38 % frente a 23 %, p = 0,2). Conclusiones: La frecuencia de MEI en esta serie es similar a lo reportado en la literatura; su presencia se asocia con una mayor gravedad de la enfermedad, mayor frecuencia de uso de biológicos y mayor tiempo de diagnóstico de la EII.

Consenso colombiano de la enfermedad inflamatoria intestinal pediátrica

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Introduction: Pediatric ulcerative colitis (CUP), pediatric Crohn's disease (PCD), and pediatric inflammatory bowel disease not classifiable (PIDNCID) have clinical and psychosocial particularities that differentiate them from those of adults and may condition different therapeutic approaches due to possible nutritional, growth and developmental repercussions, representing a challenge for the pediatrician and gastroenterologist. Objective: Develop expert consensus evidence-based recommendations for the timely and safe diagnosis and treatment of Pediatric Inflammatory Bowel Disease (PID) in children under 18 years of age for professionals caring for these patients and healthcare payers. Methodology: Through a panel of experts from the Colombian College of Pediatric Gastroenterology, Hepatology and Nutrition (COLGAHNP) and a multidisciplinary group, 35 questions were asked regarding the clinical picture, diagnosis, and treatment of PID. Through a critical review and analysis of the literature with particular emphasis on the main clinical practice guidelines (CPGs), randomized clinical trials (RCTs), and meta-analyses of the last ten years, from which the experts made 77 recommendations that responded to each of the research questions with their respective practical points. Subsequently, each of the statements was voted on within the developer group, including the statements that achieved > 80%. Results: All statements scored > 80%. PID has greater extension, severity, and evolution towards stenosis, perianal disease, extraintestinal manifestations, and growth retardation compared to adult patients, so its management should be performed by multidisciplinary groups led by pediatric gastroenterologists and prepare them for a transition to adulthood. Porto's criteria allow a practical classification of PID. In CPE, we should use the Paris classification and perform ileocolonoscopy and esophagogastroduodenoscopy, since 50% have upper involvement, using the SES-CD (UCEIS/Mayo in CUP) and taking multiple biopsies. Initial labs should include inflammatory markers and fecal calprotectin and rule out intestinal infections. Treatment, induction, and maintenance of PID should be individualized and decided according to risk stratification. Follow-up should use PCDAI and PUCAI for the last 48 hours. Immunologists and geneticists should evaluate patients with early and infantile PID. Conclusion: A consensus guideline is provided with evidence-based recommendations on timely and safe diagnosis and treatments in patients with ILD.

Guía colombiana para el diagnóstico de la deficiencia de lipasa ácida / Colombian Guidelines for Diagnosis of Lipase Acid Deficiency

Resumen Introducción: la deficiencia de lipasa ácida lisosomal (LAL-D) es una entidad de herencia autosómica recesiva que lleva a la acumulación de esteres de colesterol y triglicéridos en el hígado, bazo y otros órganos. La edad de inicio y la tasa de progresión son muy variables, lo que posiblemente sea explicado por las mutaciones presentes en el gen LIPA. Las manifestaciones clínicas son las mismas que para otras patologías hepáticas, cardiovasculares y metabólicas, lo que hace difícil reconocerla en la práctica clínica. Objetivo: proveer una guía que permita a los clínicos reconocer los principales grupos de riesgo en los cuales se debe sospechar de LAL-D y mejorar su diagnóstico. Metodología: este documento se diseñó como un consenso de expertos en el cual participaron médicos especialistas en gastroenterología, hepatología, endocrinología, genética, patología y pediatría. Se realizó una revisión de la literatura acerca de las manifestaciones clínicas y de las herramientas para el diagnóstico de LAL-D y se siguió la metodología de técnica de grupo nominal. Resultados: se generaron algoritmos diagnósticos por consenso para cada uno de los grupos de riesgo, que facilitaran la sospecha y el diagnóstico de LAL-D. Conclusiones: esta guía propone algoritmos para el diagnóstico de LAL-D con base en el consenso clínico, que buscan optimizar la ruta diagnóstica en los pacientes con dicha patología.

Abstract Introduction: Lysosomal acid lipase deficiency (LAL-D) is an inherited autosomal recessive entity that leads to the accumulation of cholesterol and triglyceride esters in the liver, spleen and other organs. The age of onset and rate of progression vary greatly, possibly explained by mutations of the LIPA gene. Clinical manifestations are the same as those of other hepatic, cardiovascular and metabolic pathologies which makes it difficult to recognize in clinical practice. Objective: The objectives of these guidelines is to help clinicians recognize the major groups at risk for LAL-D and to improve its diagnosis. Methodology: This document was designed as a consensus of experts in gastroenterology, hepatology, endocrinology, genetics, pathology and pediatrics. A review of the literature regarding clinical manifestations and tools for diagnosis of LAL-D was conducted and the nominal group technique was followed. Results: Diagnostic algorithms which facilitate suspicion and diagnosis of LAL-D were generated by consensus for each of the risk groups. Conclusions: This guide proposes algorithms for the diagnosis of LAL-D based on clinical consensus. The algorithms seek to optimize diagnosis for patients with this pathology.